Anti-respiratory syncytial virus antibodies, and methods of their generation and use

Abstract

Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as nucleic acid sequences encoding such antibodies, methods for their identification, isolation, generation, and methods for their preparation and use are provided.

What is claimed is: 
     
       1. An isolated antibody or an antigen-binding fragment thereof that specifically binds to Respiratory Syncytial Virus (RSV) F protein (F) (“anti-RSV F antibody”), wherein said antibody:
 (i) comprises a heavy chain (HC) polypeptide comprising a variable heavy (V H) chain polypeptide comprising VH CDR1, 2 and 3 polypeptides respectively comprising the amino acid sequences of SEQ ID NO: 51, 53 and 55; and a light chain (LC) polypeptide comprising a variable light (VL) chain polypeptide comprising VL CDR1, 2 and 3 polypeptides respectively comprising the amino acid sequences of SEQ ID NO: 59, 61 and 63; or 
 (ii) comprises a HC polypeptide comprising a VH chain polypeptide comprising VH CDR1, 2 and 3 polypeptides respectively comprising the amino acid sequences of SEQ ID NO: 979, 981 and 983; and a LC polypeptide comprising a VL chain polypeptide comprising VL CDR1, 2 and 3 polypeptides respectively comprising the amino acid sequences of SEQ ID NO:987, 989 and 991. 
 
     
     
       2. The isolated anti-RSV F antibody of  claim 1 , which comprises either:
 (i)
 (1) a VH chain polypeptide comprising the same VH CDRs as recited in  claim 1  (i) and possessing at least 90% sequence identity or at least 95% sequence identity to the VH chain polypeptide of SEQ ID NO: 50; and 
 (2) a VL chain polypeptide comprising the same VL CDRs as recited in  claim 1  (i), and possessing at least 90% sequence identity, or at least 95% sequence identity to SEQ ID NO: 58: or 
 
 (ii)
 (1) a VH chain polypeptide comprising the same VH CDRs as recited in  claim 1  (ii), and possessing at least 90% sequence identity, or at least 95% sequence identity to the VH chain polypeptide of SEQ ID NO: 978; and 
 (2) a VL chain polypeptide comprising the same VL CDRs as recited in  claim 1  (ii), and possessing at least 90% sequence identity to the VL chain polypeptide of SEQ ID NO: 986. 
 
 
     
     
       3. The isolated anti-RSV F antibody of  claim 1 , which comprises either:
 (i) a VH chain polypeptide comprising the amino acid sequence of SEQ ID NO: 50; and a VL chain polypeptide comprising the amino acid sequence of SEQ ID NO: 58: or 
 (ii) a VH chain polypeptide comprising the amino acid sequence of SEQ ID NO: 978; and a variable light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 986. 
 
     
     
       4. A pharmaceutical composition comprising the anti-RSV F antibody of  claim 1 ; and a pharmaceutically acceptable carrier and/or excipient. 
     
     
       5. A method for (i) preventing a respiratory syncytial virus (RSV) infection in a patient in need thereof or suspected of being in need thereof, or for treating a patient suffering from an RSV infection, or for ameliorating at least one symptom or complication associated with the infection, wherein the infection is either prevented, or at least one symptom or complication associated with the infection is prevented, ameliorated, or lessened in severity and/or duration as a result of such use; or (ii) treating or preventing either a RSV infection or a human metapneumovirus (HMPV) infection, or at least one symptom associated with the RSV infection or the HMPV infection, in a patient in need thereof or suspected of being in need thereof, by administering an anti-RSV F antibody according to  claim 1 . 
     
     
       6. The method according to  claim 5 , which further comprises administering to the patient a second therapeutic agent optionally selected from the group consisting of an antiviral agent; a vaccine specific for RSV, a vaccine specific for influenza virus, or a vaccine specific for metapneumovirus (MPV); an siRNA specific for an RSV antigen or a metapneumovirus (MPV) antigen; a second antibody specific for an RSV antigen or a metapneumovirus (MPV) antigen; an anti-IL4R antibody, an antibody specific for an influenza virus antigen, an anti-RSV-G antibody, and a NSAID. 
     
     
       7. A pharmaceutical composition comprising the anti-RSV F antibody of  claim 2 ; and a pharmaceutically acceptable carrier and/or excipient. 
     
     
       8. A pharmaceutical composition comprising the anti-RSV F antibody of  claim 3 ; and a pharmaceutically acceptable carrier and/or excipient. 
     
     
       9. A method for (i) preventing a respiratory syncytial virus (RSV) infection in a patient in need thereof or suspected of being in need thereof, or for treating a patient suffering from an RSV infection, or for ameliorating at least one symptom or complication associated with the infection, wherein the infection is either prevented, or at least one symptom or complication associated with the infection is prevented, ameliorated, or lessened in severity and/or duration as a result of such use; or (ii) treating or preventing either a RSV infection or a human metapneumovirus (HMPV) infection, or at least one symptom associated with the RSV infection or the HMPV infection, in a patient in need thereof or suspected of being in need thereof, by administering an anti-RSV F antibody according to  claim 2 . 
     
     
       10. A method for (i) preventing a respiratory syncytial virus (RSV) infection in a patient in need thereof or suspected of being in need thereof, or for treating a patient suffering from an RSV infection, or for ameliorating at least one symptom or complication associated with the infection, wherein the infection is either prevented, or at least one symptom or complication associated with the infection is prevented, ameliorated, or lessened in severity and/or duration as a result of such use; or (ii) treating or preventing either a RSV infection or a human metapneumovirus (HMPV) infection, or at least one symptom associated with the RSV infection or the HMPV infection, in a patient in need thereof or suspected of being in need thereof, by administering an anti-RSV F antibody according to  claim 3 .